Sickle cell trait (SCT) affects over 1 in 12 African Americans in the United States and nearly 300 million people worldwide. Although SCT has largely been considered a benign condition, emerging evidence suggests that acute and chronic sickling in the setting of low oxygen tension or stress may lead to clinical complications in affected carriers. In particular, the hypoxic environment of the renal medulla appears to induce local red blood cell sickling, ultimately resulting in vascular damage and chronic kidney disease (CKD). A similar process may also occur in the hypoxic venous system of the body, leading to coagulation activation and an increased risk of venous thromboembolism (VTE). The risk of both CKD and VTE appears to be higher in African Americans compared to other populations; therefore SCT may be an important and unrecognized genetic modifier of disease in this population. Dr. Naik is an Assistant Professor in the Division of Hematology at Johns Hopkins whose long-term aspiration is to become an independent investigator in sickle cell trait with the goal of developing evidence-based screening, genetic counseling, and treatment guidelines for affected individuals. The overall aims of her proposal are to elucidate the potential complications of SCT and to determine the impact of SCT on CKD and VTE risk in African Americans. She will first perform a rigorous systematic review of the published literature to identify important clinicl complications related to SCT, determine the strength of the existing literature, and identify gaps in current knowledge. Using advanced epidemiologic techniques, she will then analyze data from well-characterized cohorts with large numbers of African-American participants to characterize the risk of CKD and VTE in individuals with SCT. This research will contribute critical knowledge about the complications of SCT and will provide framework for future epidemiologic, translational, and treatment studies in SCT. In addition, with the support of this K08 Mentored Career Development Award, Dr. Naik will integrate a well-rounded, multi-disciplinary mentorship team, a focused training plan, and an innovative research strategy to ensure her successful transition to an independent investigator.